Method and composition for the control of coccidiosis in animals



United States Patent Ofifice 3,li52,602 METHGD AND CGMPOSHTEON FOR THE CGNTRQL OF CDOCIIDEOSHS EN ANIMALS Theo Alfred Hymas and Graham Thomas Stevenson,

Midland, Mich, assignors to The Dow Chemical Company, Midland, Mich, a corporation of Delaware No Drawing. Filed Get. 1, 1956, Ser. No. 612,917 9 Claims. (Cl. 161-531) This invention relates to animal husbandry and more particularly to a method and composition for the control of gastro-intestinal parasites in animals and for improving the efficiency of the utilization of animal feed.

Domestic animals are subject to attack by various types of gastro-intestinal parasites. Certain of these parasites are minute protozoan organisms known as coccidia. These protozoan organisms are the causative agents of coccidiosis which is a widespread and destructive disease of chickens, ducks, pigeons, geese and turkeys. The disease is also found in pigs, dogs, lambs, calves and other domesticated animals.

The coccidia invade and multiply in various organs of their host but particularly in the gastro-intestinal tract. During the process of growth and multiplication they erode the epithelial tissue of the cecum and intestines bringing about anemia, weakness, hemorrhage, digestive disturbances and intestinal necrosis. If the animals do not die from the infection, they are often rendered economically valueless by chronic forms of the disease.

Several remedies have been suggested for the control of these gastro-intestinal parasites. These remedies are generally administered through the water or feed of the animals. Many of these materials are inefiicient while others are too expensive or too toxic for prophylactic administration. One difiiculty encountered with materials used in the past has been the adverse effect which some of these materials have had upon growth, reproduction and fertility. Another difliculty has been the poisoning of the blood-forming organs by some of these remedies and a drastic reduction in the number of red and white blood cells in the body. A further difficulty has been the inability of many materials to control more than one species of coccidia or to control the various strains of coccidia within one species. These effects have made the use of many remedies hazardous and unprofitable.

It is an object of the present invention to provide a new and improved practice for raising and benefiting animals and fowl. A further object is to provide a new and improved method for the control of gastro-intestinal parasites in animals. An additional object is the provision of a method of improving the utilization of feed by animals. Another object is to provide a novel method for the control of coccidiosis in infected animals. Still another object is to provide a method which may be employed prophylactically to control parasitic diseases of the gastro-intestinal tract of animals without adversely affecting the metabolic activity, reproduction, or the bloodforming organs of animals so treated. A further object is to provide novel feed compositions adapted to be employed in the new methods in animal husbandry. Other objects will appear throughout the following specification and appended claims.

The new method comprises administering to animals a polynitrobenzamide compound having the formula i ZOR wherein R represents a radical selected from the group consisting of amino, monomethylamino, dimethylamino, monoethylamino, diethylamino, propylamino, dipropylamino, allylamino, hydroxyethylamino, hydroxypropyl- EfiSZfiilZ Patented Sept. 4, 15362 amino, methoxyethylamino, and methoxypropylamino and Z represents a substituted phenyl radical selected from the group consisting of OzN OZN I O O OzN O2N X and in which X represents a member of the group consisting of hydrogen, amino, lower alkoxy and lower alkyl and Y represents a member of the group consisting of hydrogen, lower alkoxy and lower alkyl. In the present specification and claims the expressions lower alkoxy and lower alkyl refer to the alkoxy and alkyl radicals containing from 1 to 3 carbon atoms, inclusive. Such practice improves the efficiency of the utilization of feed by animals and protects the animals from parasitic diseases of the gastro-intestinal tract and particularly from coccidiosis. Further, the practice protects the animals from many strains of Eimeria tenella coccidia. Also, while protecting the animals from coccidiosis, the practice allows the protected animals exposed to the coccidial infection to develop acquired immunity to the disease. The polynitrobenzamide compounds are crystalline solids and inexpensive to prepare. They are not repellent to animals and may be employed in admixture with animal feed. They may be administered continuously or intermittently in dosages suflicient to improve feed efiiciency and to control gastro-intestinal parasites in infected animals without adversely affecting the metabolic activity, reproduction or the blood-forming organs of the fowl, or without imparting any unpalatable characteristics to animal flesh.

The oral administration or feeding of an effective dosage of the polynitrobenzamide compounds is essential and critical for the practice of the present invention. In general, good results are obtained when the animals are fed a daily dosage of from 3 to 2,000 milligrams of the polynitrobenzamide compounds per kilogram of body weight. Where prophylactic treatment for the control of gastro-intestinal parasites is desired and the compounds are fed continuously, daily oral dosages of from 3 to 250 milligrams per kilogram of body weight have been found to be satisfactory. Where danger of reinfestation from contaminated feed or surroundings is low, good controls are obtained when the infected animals are fed a daily dosage of 35 milligrams or more per kilogram of body weight for a period of from 2 to 5 days.

The method of the present invention may be carried out by the oral administration or feeding of the unmodilied polynitrobenzamide compounds. However, the present invention also embraces the employment of a liquid, powder, mash, pellet or other animal feed composition containing said compounds. In such usage, the compounds may be modified with one or more of a plurality of additaments or innocuous ingestible adjuvants including water, ethanol, skim milk, edible oils, syrups, surface active dispersing agents such as the liquid and solid emulsifying agents, and edible solid carriers such as edible powders and commercial animal feeds, concentrates or supplements. By commercial animal feeds, concentrates or supplements are meant the partial and complete animal feeds containing desirable amounts of minerals, vitamins, antioxidants, antibiotics and growth stimulants. Such compositions are adapted to be fed to animals to supply the desired dosage of active agent or to be employed as concentrates and subsequently diluted with additional carrier to produce the ultimate compositions. The exact concentration of the polynitrobenzamide compounds to be employed in the compositions may vary provided that enough of the composition is ingested by the animal so as to provide the required internal dosage of active ingredient. For example, where direct administration to the individual animal is preferred, liquid or solid compositions containing from 5 to 95 percent by weight of the agents may be employed to supply the desired dosage. Where the compounds are provided as a constituent of the principal food ration, satisfactory results are obtained with food rations containing a minor but eifective amount of the polynitrobenzamide compounds. The exact amounts of the compounds in the ration are dependent upon the food consumption and feeding habits of the animal concerned. In fowl the required dosages may be supplied with mash compositions containing from 0.001 to 0.1 percent by weight of the active agents. In pigs, the required dosage may be supplied with mash compositions containing from 0.001 to :1 percent by weight of active material .When fed as the principal food ration. Where the compounds are furnished in the drinking water, good results are obtained at concentrations of the agents in the water equal to one-half those employed when the compounds are supplied as a constituent in the principal food ration. In compositions to be employed as concentrates,- the active agents may be present in a concentration of from to 95 percent by weight.

Liquid compositions containing the desired amount of the polynitrobenzamide compounds may be prepared by dissolving the compounds in ethanol, propylene glycol, or an edible oil or by dispersing them in water with the aid of a suitable surface active dispersing agent such as an ionic or non-ionic emulsifying agent. Suitable surface active dispersing agents include the glycerol and sorbitan esters of fatty acids and the polyoxyalkylene deor dispersed in an animal feed and such feed used to supply a part or all of the ration. Alternatively, the polynitrobenzamide compounds may be dissolved in an organic solvent such as alcohol or acetone and the resulting mixture dispersed in an animal feed which is then dried to remove the solvent. The compounds may also be dispersed in an edible oil such as coconut, olive, cotton seed or peanut oil and the resulting mixtures dispersed in the feed. These edible oil compositions may contain one of the aforementioned emulsifying materials as a dispersing agent.

The following examples illustrate the invention but are not to be construed as limiting:

Example I Twenty-five parts by weight of various 3,5-dinitro-2- methylbenzamides were separately ground with parts of fullers earth to prepare compositions adapted to be fed to animals or employed as dispersible concentrates. Each such composition contained only one 3,5-dinitro- Z-methylbenzamide compound. A portion of each of these compositions was dispersed in a commercial poultry starting mash to produce medicated feed compositions containing various amounts of one of the benzamide compounds.

Portions of these medicated feed compositions and unmodified starting mash were fed as a sole ration to groups of chickens of the same history. Each such test group consisted of 15 white Leghorn chicks which were seventeen days old. Twenty-four hours after the initiation of the diets, 40,000 sporulated Eimeria necatrix oficysts were introduced directly into the crops of the birds. At the time of the initiation of the diets and from the fourth through the tenth day thereafter, the birds were weighed and the average weight per bird for each test group determined. During the interval between the fifth and seventh days, the coccidial infection generally causes maximum disturbances in the rate of growth. Another group of birds was left untreated and uninoculated to serve as an uninfected check. Any birds which died were autopsied and the cause of death determined. The average Weights per hird at the aforementioned intervals and the mortaility figures for each test group are shown in the following table.

aqueous compositions may contain one or more water immiscible oils as a solvent for the active agent. In such compositions the water, oil and emulsifying agent con- 'stitute an aqueous emulsion carrier.

In the preparation of solid feed compositions, the polynitrobenzamide compounds may be mechanically ground -with an edible solid such as oyster shell flour or a solid,

70 mals or employed as dispersible concentrates.

Percent by Average Weight Per Bird in Grams on Day Percent Q-Methyl-Benzamide Agent Weight of Indicated After Diet Began Mortality Employed Active From Agent Goccidiosis 3753mm" i 0. 02 114 157 169 183 194 205 221 234 0 fig 160 172 18; 194 204 219 232 0 N'EthYL315'Dm1tm 0. g 112 15g 178 187 197 208 220 239 0 i 0. 02 114 154 168 182 193 202 219 232 0 N-(2-Methoxy-ethyI)-3,5-

Dinitro- 0.02 114 155 168 181 183 190 215 224 0 N-(2- ydroxy-propyl)-3,5-

Dinitro- 0. 02 115 156 171 194 205 223 23s 0 N-(2-Hydroxyethyl)-3,5

Dinitro- 0. 02 114 152 155 176 179 185 203 212 0 Infected Checks 115 156 155 150 150 137 145 161 33 Uninfected Check 115 158 171 183 190 200 218 231 0 'rivatives of fatty alcohols and of sorbitan esters. The Example 2 Twenty-five parts by weight of various 3,5-dinitrobenzamides were separately ground with 75 parts of bentonite to prepare compositions adapted to be fed to ani- Each such composition contained only one benzam ide compound. A portion of each of these compositions was dispersed in a commercial poultry starting mash to produce medicated feed compositions containing 0.015 per- 'may be administered in the form of capsules or tablets 75 cent by weight of one of the benzamide compounds.

These medicated feed compositions and unmodified starting mash were fed as a sole ration to groups of chickens of the same history. Each such test group consisted of white Leghorn chicks which were sevencontaining 0.0125 percent and 0.015 percent of 3,5-dinitro-Z-methylbenzamide. These compositions and unmodified mash were fed as a sole food ration to groups of white Leghorn chickens of the same history and past em teen days old. Twenty-four hours after the initiation of 5 'f E h uch test group consisted of birds the diets, 35,000 sporulated Eimerirz necatrix oticysts e w e Seventeen a Twemy'fmllr hours, after were introduced directly into the crop of each bird. Folthe i ef of 2 g aq i Elmlel lowing the inoculation the birds were observed for ten g g i fi i i f .2? O g i jli days for mortality due to coccidial infection. During this 6 If lmu aneous W1 6 1m Ion 0 e r s eriod coccidial infection enerall causes the eater 10 and from the fourth thlough the tenth day the/matter p 1 f Hi i i y i the birds were weighed and the average Weight per bird prfopor on o mo a 1-es.1 d group 0 S was for each test group determined. All birds which died e t untreated e c 9 Serve as Inflected were autopsied to ascertain whether death was due to eheek- Au buds Winch dled were autopsied and the coccidiosis. The results of this experiment are shown in cause of death determmed. The percent mortaility figures 15 the follgwing tabla Average Weight Per Bird in Grams on Day Percent Percent by Weight of Indicated After Diet Began Mortality 3,5 Dinitro-2 -meth- From Cocylbenzamide in Feed cidiosis 0.0125 101 110 149 159 166 176 192 204 0 0.015 98 139 143 100 169 179 197 210 0 Infected Control 99 139 149 147 132; 141 157 170 Umnfected Control 148 161 171 185 203 216 0 for each test group are set forth in the following table. Example 5 Example 3 Portions of the concentrate compositions as prepared in Example 1 were dispersed in chicken mash to prepare medicated feed compositions containing 0.02 percent by weight of one of the 3,5-dinitro-2-rnethylbenzamide com- Mash compositions were prepared as described in Example 4 containing various amounts of 3,5-dinitro-2- methylbenzamide. These medicated feed compositions and unmodified poultry mash were fed as a sole ration to groups of 15 chickens each having the same history and past environment. All the chickens were seventeen days old. Twenty-four hours after the initiation of the diets 50,000 Eimeria necatrix oocysts were introduced directly into the crops of the birds. The average weight of each bird was recorded upon the initiation of the diet and on the fourth through the tenth day thereafter. The percent by weight of active agent in the diet, the average Weight per bird in each test group and the mortality from coocidiosis are shown in the following table.

Average Weight Per Bird in Grams on Day Percent Percent by Weight of Indicated After Diet Began Mortality 3,5 Dim'tro 2 meth- From Cocylbenzamide in Feed cidiosis 0.025 107 147 158 167 177 188 100 207 0 0.01. 107 149 162 173 184 196 208 224 0 0.005.. 106 152 163 186 195 207 222 0 Infected Control-.. 107 153 161 153 147 129 132 147 73 Uninfected Control. 108 152 163 175 186 200 211 223 0 pounds. These medicated feed compositions were tested Example 6 with unmodified mash in a manner similar to that described in Example 1. In such operations, each test group consisted of 15 birds and the birds were inoculated with 50,000 sportulated Eimeria tenella oocysts. The average Weight per bird and the percent mortality from coccidiosis in each test group are set forth in the following table.

A dispersible concentrate of 3,S-dinitro-Z-methylbenzamide prepared as described in Example 1 was dispersed in a commercial poultry mash to produce medicated feed compositions containing 0.015 percent and 0.01 percent of 3,5 dinitro-Z-rnethylbenzam-ide. These medicated feed compositions and unmodified poultry mash were fed as a sole ration to flocks of White Rock chickens of the same Average Weight Per Bird in Grams on Days Per ent 2-Mcthylbenzam1de Indicated After Diet Began Mortality Agent Employed From Coccidiosis 0 4 5 e 7 3 9 10 3,5-Dinitro- 136 131 195 206 213 228 242 254 0 N-Methyl-3,5-Dinitro- 139 133 199 211 217 223 243 25s 0 N,N Dimethyl 3,5

Dinitro- 184 200 211 216 232 248 263 0 Infected Control 136 176 202 196 184 185 194 203 20 Uninfected Control. 136 184 198 211 220 235 253 269 0 Example 4 history and past environment. Each flock consisted of A portion of the concentrate composition containing 81 cockerels and 8 1 pullets which were one day old. 25 percent by weight of 3,S-dinitro-Z-methylbenzamide The flocks were kept in separate rearing pens and mainas prepared in Example 1 was dispersed in commercial tained upon cane litter in accordance with sanitary poultry poultry mash to prepare medicated feed compositions 75 practices. Upon the 23rd day following initiation of the diets, all the birds were fed a mash heavily inoculated with the sporulated oticysts of Eimeria tenella and Eimeria necatrix. The inoculated ration was fed in an amount sufiicient to provide 150,000 oocysts per bird. Following the feeding of the inoculated ration, any of the birds which died were autopsied and the cause of death determined. Eight weeks after the initiation of the diets, the birds were Weighed and the average weight per bird for each test flock determined. The nature of the diets, the average weights of the birds and the mortality figures are set forth in the following table.

Example 7 Ninety parts by weight of 3,5-dinitro-4-methoxybenzamide, 3,S-dinitro-4-propylbenzamide, 4,6-dinitro-2- methoxy-benzamide or N-ethyl-3,5-dinitro-4-ethylbenzarnide are mechanically ground with bentonite to produce parasiticidal concentrates containing 90 percent by weight of one of the benzamide compounds.

In a similar manner, medicated feed supplements are prepared by grinding together 50 parts N,N-diisopropyl- 3,5-dinitro-2-methylbenzamide, 4,6-dinitro-3-ethylbenzamide, N-methyl-3,S-dinitro-2-propoxy-benzamide or N- methyl-4,6-dinitro-2-methylbenzamide with 1 part of a sor'oitan monopalmitate (Span 20) and 49 parts of attapulgite clay.

In another operation, 20 parts by weight of N-methyl- 2,4,6-trinitrobenzamide is mechanically mixed with 80 parts of soybean meal to prepare a medicated animal feed concentrate.

In still another operation, parts by weight of N-ethyl- 4,6-dinitro-Z-propylbenzamide, N-allyl-Z,4-dinitrobenzamide or N,N-dimethyl-2,4-dinitrobenzamide are dispersed in 90 parts of cottonseed oil to prepare edible oil concentrate compositions containing one of the benzamide compounds.

These compositions are adapted to be administered to animals to supply the desired internal dosage of polynitrobenzamide compound or to be employed as concentra-tes and subsequently diluted with additional edible carriers to produce animal feeds containing the desired amount of active agent.

Example 8 The 3,5-dinitro-2-methylbenzamide concentrate as described in Example 1 was dispersed in a commercial poultry mash to prepare medicated feed compositions containing various amounts of said compound. These compositions and unmodified mash were fed as a sole food ration to groups of chickens of the same history and environment. Each such test group consisted of 100 White Rock cockerels and 100 White Rock pullets which Were one day old. The groups were maintained on wire in heated steel cages and under conventional sanitary poultry practices to minimize the possibility of exposure to coccidial infection. Just prior to the initiation of the diets and four weeks and eight weeks thereafter, the birds were weighed and the average weight per bird for each test group determined. During the eight weeks period, a record Waskept of the feed consumed by each test group. The average weight per bird for the test groups and the feed efiiciency factor are set forth in the following table.

The feed efiiciency factor is the number of grams of feed eaten per gram of body weight gained.

Average Weight Per Bird in Grams at the indicated int Percent by weight of 3,5- tervals following initiation of Feed Dinitro-2-Methylbenz- The Diets Efliciency amide in lvlash Factor 0 Weeks 4 Weeks 8 Weeks Example 9 3,5-dinitro-Z-methylbenzamide was dispersed in a commercial pig feed to prepare medicated feed compositions containing from 0.01 to 0.03 percent of said compound. These compositions and the unmodified feed were fed as a sole food ration to groups of pigs of the same history and environment. Each such test group consisted of five young pigs having an average weight of 24 pounds. These pigs were maintained on the experimental diets for a period of ten weeks after which time they were again weighed to determine which group had gained the mos-t Weight. The results of this experiment are recorded in the table below.

Example 10' Twenty-five parts by weight of various polynitrobenzamides were separately ground with parts of fullers earth to prepare dispersible concentrates containing only one of said compounds. A portion of each of these corm positions was dispersed in a commercial poultry mash to produce medicated feed compositions containing various amounts of one of the test compounds. These compositions and unmodified mash were fed as a sole feed ration to groups of chickens of the same history. Each test group consisted of three chickens which were seventeen days old. One day after the diets were begun, from 30,000 to 100,000 sporulated Eimeria necatrix oiicysts were introduced directly into the crop of the birds. Another group of birds was left untreated and uninoculated to serve as an uninfected check. Seven days following the initiation of the diets, the birds were sacrificed, autopsied and an examination made to determine the percent control of coccidial disease. The percent by weight of each compound in the feed and the percent control of coccidiosis are shown in the following table.

X All birds heavily infected with coccidial disease. 2 N o coccidial disease The polynitrobeuzamides as employed in accordance with the present invention are crystalline solids which are somewhat soluble in many organic solvents and of very low solubility in water. The 2,4,6-trinitrobenzamides, 3,5-dinitrobenzamides and 2- and 4-alkyl-3,5- dinitrobenzamides may be prepared by the reaction of 2,4,6-trinitrobenzoic acid, 3,5-dinitrobenzoic acid or a 2- or 4-alkyl-3,S-dinitrobenzoic acid with thionyl chloride (SOCl or phosphorus pentachloride to produce the corresponding acid chlorides. The acid chlorides are then reacted with at least 2 moles of aqueous ammonia or a suitable amine per mole of acid chloride to obtain the desired polynitrobenzamide or N-substituted polynitrobenzamide compounds.

The 4,6-dinitrobenzamides and 2- or 3-alkyl-4,6-dinitrobenzamides may be prepared by diazotization of 4,6- dinitroaniline or a 2- or 3-alkyl4,6-dinitroaniline to form the corresponding diazonium salt which is then reacted with cuprous or nickelous cyanide to obtain the corresponding nitrile. Subsequent hydrolysis of the nitrile results in the formation of the corresponding polyni-trobenzoic acid. The acid is then reacted with thionyl chloride to obtain the acid chloride which is reacted with ammonia or a suitable amine to produce the desired benzamide compound.

In an alternative procedure, the 2- or 3-methyl-4,6-dinitrobenzamides may be prepared by oxidizing 1,2-dimethyl-4,6-dinitrobenzene or 1,3-dimethyl-4,6-dinitrobenzene with dilute nitric acid whereby the 2- or 3-methyl-4,6-dinitrobenzoic acids are produced. The latter acids may be treated as previously described to obtain the desired benzamide compounds.

The 2- or 4-amino-3,S-dinitrobenzamides are prepared by the nitration of 2-chlorobenzoic acid or 4-ch1orobenzoic acid to obtain the corresponding 3,5-dinitro-chlorobenzoic acids which are then reacted with phosphorus pentachloride to form the corresponding acid chlorides. These acid chlorides are then reacted with aqueous ammonia or a suitable amine in the proportion of two moles of ammonia or amine per mole of acid chloride. Since the acyl chlorine is more reactive than the ring chlorine, such reaction results in the formation of 2- or 4-chloro-3,5-dinitrobenzamides or N-substituted 2- or 4-chloro-3,5-dinitrobenzamides. The latter benzamide compounds thereafter may be reacted with excess alcoholic ammonia to replace the ring chlorine and obtain the desired 2- or 4- amino-3,5-dinitrobenzamide compounds.

The 2-amino-4,6-dinitrobenzamides may be prepared by the reduction of 2,4,6-trinitrobenzamide with sodium sulfhydrate (NaSH), whereby the ortho nitro group is selectively reduced to an amino group.

The 2-or 4-allcoxy-3,S-dinitrobenzamides may be prepared by the reaction of a 2- or 4-chloro-3,5-dinitrobenzamide or an N-substituted-2- or 4-chloro-3,5-dinitrobenzamide with an alkali metal alkoxide whereby an alkoxy group is substituted for chlorine in the 2- or 4-chloro-3,5- dinitrobenzamide compound.

The 2- or 3-alkoxy-4,6-dintrobenzamides or N-substituted-2- or 3-alkoxy-4,6-dinitrobnzamides may be prepared by the diazotization of a 2- or 3-alkoxy-4,6-dinitroaniline to form the corresponding diazonium salt which is then reacted with cuprous or nickelous cyanide to obtain the corresponding nitrile. The nitrile is thereafter hydrolyzed to the corresponding benzoic acid, the benzoic acid converted to the acid chloride and the acid chloride reacted with ammonia or an amine as previously described to obtain the desired benzamide compounds.

We claim:

1. In the practice of animal husbandry, the method 10 which comprises orally administering to animals a compound having the formula wherein R represents a radical selected from the group consisting of amino, monomethylamino, dimethylamino, monoethylamino, diethylamino, propylamino and diproplyamino, and X represents a member of the group consisting of methyl and ethyl, said compound being employed daily in an amount of from 3 to 2,000 milligrams per kilogram of body weight.

2. A method claimed in claim 1 wherein the polynitrobenzamide compound is fed daily in an amount of from 3 to 250 milligrams per kilogram of body weight.

3. A method claimed in claim 1 wherein the polynitrobenzamide compound is 3,5-diuitro-2-methylbenzamide.

4. A method claimed in claim 1 wherein the polynitrobenzamide compound is N-isopropyl-3,5-dinitro-2-methylbenzamide.

5. A method claimed in claim 1 wherein the polynitrobenzamide compound is N-methyl-3,S-dinitro-Z-methylbenzamide.

6. A poultry feed containing from 0.001 to 0.1 percent by weight of 3,5-dinitro-2-methylbenzamide.

7. A poultry feed containing from 0.001 to 0.1 percent by weight of N-methyl-3,S-dinitro-Z-methylbenzamide.

8. A method which comprises feeding an animal a composition comprising as an active ingredient a compound corresponding to the formula X O Q- wherein R represents a radical selected from the group consisting of amino, monomethylamino, dimethylamino, monoethylamino, diethylamino, propylamino and dipropylamino, and X represents a member of the group consisting of methyl and ethyl, in intimate admixture with an inocuous ingestible adjuvant, the composition being fed in an amount sufiicient to provide a daily dosage of from 3 to 2,000 milligrams of said compound per kilogram of body weight.

9. An animal feed containing from 0.001 to 0.1 percent by weight of a compound corresponding to the formula wherein R represents a radical selected from the group consisting of amino, monomethylamino, dimethylamino, monoethylamino, diethylamino, propylamino and dipropylamino, and X represents a member of the group consisting of methyl and ethyl.

References Cited in the file of this patent Thompson: Chem. Abst., vol. 41, 1947, pages 3902, 3903, 3909i. 

1. IN THE PRACTICE OF ANIMAL HUSBANDRY, THE METHOD WHICH COMPRISES ORALLY ADMINISTERING TO ANIMALS A COMPOUND HAVING THE FORMULA 